Dehydroepiandrosterone (DHEA) is a major adrenal secretory product in men and women, yet it has no known biological function. On the basis of a 10-year prospective study involving over 5000 apparently healthy women, Bulbrook et al. concluded that women with subnormal excretory rates of androsterone and etiocholanolone (metabolites of DHEA) experience an increased risk of breast cancer. It is well documented that DHEA is a potent non-competitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PD). Yen et al. found that long-term treatment of mice with DHEA reduces weight gain without suppressing appetite, presumably by inhibiting lipogenesis by reducing NADPH levels as a result of inhibition of G6PD. We have found that long-term treatment of C3H-Avy/A (obese) and C3H-A/A (non-obese) mice with DHEA, in addition to reducing weight gain without suppressing appetite, markedly inhibits the development of spontaneous breast cancer and delays the rate of aging. We have since observed that DHEA is a potent anti-tumor promoter, and antagonizes the epidermal cell hyperplasia and enhancement in the rate of DNA synthesis when phorbol esters are applied to mouse skin.